Lecture 5: The Human Genome Project PDF

Lecture 5 – The Human Genome Project and how we got there Part 1 – We live in a post genomic age The Human Genome Project: Rough drafts were published in 2001, First complete draft of sequence was reported on April 14, 2003 The goals of the HGP 1. Identify all of the gene in huma...

Lecture 5 – The Human Genome Project and how we got there Part 1 – We live in a post genomic age The Human Genome Project: Rough drafts were published in 2001, First complete draft of sequence was reported on April 14, 2003 The goals of the HGP 1. Identify all of the gene in human DNA 2. Determine the sequence of the DNA base pairs that make up the human genome 3. Store this information in databases 4. Improve tools for data analysis 5. Transfer related technologies to the private sector, and 6. Address the ethical, legal and social issues that may arise from the project. No of protein coding genes 22,000 protein coding genes found Only 1.5% of total genome is protein coding. Benefits of HGP Understanding our evolutionary history (Human and chimpanzee genomes can be compared to identify genes that contribute to unique human traits) (two chimpanzees' chromosomes are fused in us) Personalised medicine (if a drug is toxic or beneficial to an individual or not) Imoroved genetic screening: if we can identify functions of all our genes then medicine might become: PREDICTIVE, PREVENTATIVE AND PERSONALISED. Ethical and legal issues Will genetic information be used fairly? Could an employer refuse to hire someone because of a health concern indicated by that person’s genome? Could health insurance companies refuse to provide insurance to some people? Psychological impact: imagine you have a genotype associated with a short life – do you want to know? Stigmatisation: do you want your neighbor to know? Part 2 – the discovery of hereditary ‘factor’ 1958, Francis Crick – Central Dogma of Molecular Biology Transfer of information from DNA via RNA intermediate to protein State that once information is in protein form it cannot be transferred back. ‘DNA makes RNA makes Protein’ The central Dogma also recognised that DNA replication and RNA replication also transfer information but also considered other routes of information flow, although at the time these were not supported by experimental evidence. The Central Dogma revisite 1. DNA replication – information held at the DNA level is copied (E.g. cell division) 2. Transcription – information copied into RNA 3. Translation – information translated into protein 4. Reverse transcription – information held at the RNA level is copied into DNA (E.g. retroviruses) 5. RNA replication – information held at the RNA level is copied (e.g. RNA viruses) Gregor Mendel – the founder of genetics Demonstrated that the inheritance of certain traits in pea plants follows particular patterns, now referred to as the laws of Mendelian inheritance. Experimented with peas (Pisum Sativum) Why: Produce large number of offspring Short lifespan Can self-pollinate and cross pollinate Pure breeding lines with contrasting characteristics Simple tools are needed This was unexpected: the general view was that characters were BLENDED Mendel called YELLOW pea colour a Dominant trait. Test cross: the next generation Used to find unknown alleles of a trait by crossing with parent individuals with recessive version of same trait. Pure green pea mate with pure yellow pea and made F1 yellow which contains all yellow peas. Also F1 yellow mate with pure green peas and made a mixture of green and yellow peas: overall, a 1:1 ratio. Despite not being visible in the F1, the green pea trait was still there, just masked by the yellow trait and again, no blending of characteristics. Mendel called Green a Recessive trait. First Law of Inheritance – the Law of Segregation Two factors for each trait from each parent  If the factors are identical, the individual is homozygous for the trait. If the factors are different, the individual is heterozygous The alternative forms of a factor = allelomorphs (nowadays, alleles). Two coexisting alleles of a trait get segregated during gamete formation, so a gamete gets only one of two alleles. Offspring receives one allele for each trait from each parent. Whichever allele is dominant determines how the trait is expressed. Part 3 –Genes reside on chromosomes 1902: the chromosome theory of inheritance – Walter Sutton Cells from female grasshoppers: 22 chromosomes plus an XX pair (24 total) Cells from males: 22 chromosomes plus an X (denoted as X0) (23 total) Sperm and eggs contain 11 chromosomes +/- an X Sutton concluded that sex was determined via chromosome –based inheritance  \ 1:1 ratio and behaviour as Mendel’s factor He proposed that Mendel’s ‘factors’ were carried on chromosomes. ‘I may finally call attention to the probability that the association of paternal and maternal chromosomes in pairs and their subsequent separation during the reducing division as indicated above may constitute the physical basis of the Mendelian law of heredity.’ The discovery of sex-linked inheritance In 1910, Morgan spotted this: wild type fruit flies have red eyes but some of his mutant flies had white eyes These results were unexpected: nonreciprocal (unlike Mendel’s crosses).